Recent studies have revealed that under conditions in which an animal's metabolic demands for calcium are readily met, the distal small intestine may become the site of an active secretory process for this divalent cation. The mechanisms underlying the regulation of this calcium secretory phenomen remain obscure. Furthermore, the role of this process in the homeostasis of other metals is not known. The purpose of the present investigation is to evaluate the potential role of factors such as vitmain D, cyclic nucleotides and certain hormones in the regulation of intestinal calcium secretion. In addition, attempts will be made to define the relative contributions of changes in the active (cellular) and diffusional (cellular and extracellular or shunt) pathways to the regulation of this secretory flux. Finally, the role of the ileum as an excretory organ for iron, strontium and other trace metals will be assessed. In order to accomplish these ends, studies of the effects of vitamin D, cyclic nucleotides, calcitonin, parathyroid hormone, and ATPase inhibitors on the movement of calcium, sodium and chloride into and across rat ileal mucosa will be undertaken. The proposed studies will involve measurements of influx at the luminal surface and bidirectional transmural fluxes with the mucosa short-circuited and clamped at various transmural potential differences. With these techniques one should be able to define the nature of the factors regulating intestinal calcium secretion, and the pathways through which calcium crosses the intestine. Finally, the importance of the ileum in maintaining the balance of other polyvalent metals will be assessed by measuring their transmural fluxes under short-circuited conditions.